Studies are proposed to execute a convergent, optically active synthesis of the milbemycins, a class of pesticidal antimicrobial agents. This synthesis will serve to develop methods which can be applied to the synthesis of the extremely potent, broadspectrum anthelminthic agents, the avermectins. These compounds have shown in vivo activity against a variety of parasitic infections in doses as low as 10 Mug/kg. Due to the wide spread nature of parasitic infections in the world today, these compounds could be of great biological importance. Methods which will be developed to allow syntheses of these classes of compounds include a stereoselective conjugate addition to spirocyclic oxaenones, a chelation directed epoxide opening, and an asymmetric Diels Alder reaction. These methods should find broad use in organic synthesis of macrolide antibiotics and other important compounds.